Atypical antipsychotics do not have a significant benefit compared with first-generation antipsychotics when a medication change is needed for patients with schizophrenia, according to an article in the October issue of Archives of General Psychiatry.

Claims that second-generation antipsychotics are more effective than first-generation drugs have shifted treatment patterns away from use of first-generation medications, although research directly comparing the drug classes has had mixed results.

Peter B. Jones, MD, PhD, University of Cambridge, England, and colleagues studied 227 patients age 18 to 65 years: "The key question was whether the additional acquisition costs of second-generation antipsychotics over first-generation antipsychotics would be offset by improvements in health-related quality of life or savings in the use of other health and social care services in people with schizophrenia for whom a change in drug treatment was being considered for clinical reasons, most commonly suboptimal efficacy or adverse effects."

Participants were randomized to receive one class of drug or the other. Physicians determined which specific medication would be best for each patient. Participants were assessed before and 12, 26, and 52 weeks after the change in treatment using a quality of life scale, with higher scores reflecting better quality of life.

The researchers estimated that second-generation antipsychotics would produce a five-point improvement in quality of life scores compared with first-generation antipsychotics. Symptoms, side effects, treatment costs and satisfaction with the drug were also measured.

Of the 227 patients, 118 (52 percent) were randomized to first-generation medications and 109 (48 percent) to second-generation medications. After 12 weeks, quality of life scores averaged 49.2 for the first-generation group and 46.6 for the second-generation group; after 26 weeks, 49.2 for first-generation and 50.4 for second-generation; and after one year, 53.2 for first-generation and 51.3 for second-generation.

"Participants in the first-generation antipsychotic arm showed a trend toward greater improvements in Quality of Life Scale and symptom scores," the authors wrote. "Participants reported no clear preference for either drug group; costs were similar."

Although surprising, these results align with other recent studies performed in the United States, they continued. "All the data suggest that careful prescribing of first-generation antipsychotics, at least in the context of a trial, is not associated with poorer efficacy or a greater adverse effect burden, both of which would translate into lower quality of life in the medium term. This suggests that despite recent policy statements and prescribing patterns, further randomized and other evaluations of second-generation antipsychotics would still be useful in establishing their role in the long-term management of schizophrenia and, likewise, the continued role of older drugs."

In a commentary, Jeffrey A. Lieberman, MD, of Columbia University Medical Center, New York, wrote that the current article and other recent findings suggest that despite their tremendous advantage in market share, second-generation antipsychotic drugs may not be much more effective than first-generation antipsychotic agents.

An objective view "must lead to the conclusion that with the possible exception of clozapine, the second-generation antipsychotics are not the great breakthrough in therapeutics they were once thought to be; rather, they represent an incremental advance at best. This underscores the urgent need for greater progress in developing novel therapeutics for schizophrenia and related psychotic disorders."